PT  - JOURNAL ARTICLE
AU  - Xavier Rovira-Clavé
AU  - Alexandros P. Drainas
AU  - Sizun Jiang
AU  - Yunhao Bai
AU  - Maya Baron
AU  - Bokai Zhu
AU  - Maxim Markovic
AU  - Garry L. Coles
AU  - Michael C. Bassik
AU  - Julien Sage
AU  - Garry P. Nolan
TI  - Spatial epitope barcoding reveals subclonal tumor patch behaviors
AID  - 10.1101/2021.06.29.449991
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.06.29.449991
4099  - http://biorxiv.org/content/early/2021/06/30/2021.06.29.449991.short
4100  - http://biorxiv.org/content/early/2021/06/30/2021.06.29.449991.full
AB  - Intratumoral variability is a seminal feature of human tumors contributing to tumor progression and response to treatment. Current technologies are unsuitable to accurately track phenotypes and subclonal evolution within tumors, especially in response to genetic manipulations. Here, we developed epitope combinatorial tags (EpicTags), which we coupled to multiplexed ion beam imaging (EpicMIBI) for in situ tracking of barcodes within tissue microenvironments. Using this platform, we dissected the spatial component of cell lineages and phenotypes in a xenograft model of small-cell lung cancer. We observed emergent properties from mixed clones leading to the preferential expansion of subclonal patches for both neuroendocrine and non-neuroendocrine cancer cell states in this model. In tumors harboring a fraction of PTEN-deficient cancer cells, we uncovered a non-autonomous increase of subclonal patch size in PTEN wildtype cancer cells. EpicMIBI can facilitate in situ interrogation of cell-intrinsic and cell-extrinsic processes involved in intratumoral heterogeneity.Competing Interest StatementJ.S. receives research funding from Pfizer. G.P.N. is co-founder and stockholder of Ionpath, Inc. and inventor on patent US 2019/0162729. The other authors declare no competing interests.